Latest / BioSpace / Novartis’ and BMS’ paused CAR T trials, RevMed’s pancreatic cancer approval, more MFN deals
Transcript
- Jef: Hello, and welcome to Biospaces the Weekly. I'm your host, Jeff Axt, and we've got a full show for you today. The biggest news so far this week is the pauses of several CAR T trials and autoimmune disease. Three patients died after taking Novartis's candidate Rep cell, prompting the company to suspend several ongoing studies. Meanwhile, Bristol Meyer Squibb also picked up some concerning safety signals for its own CAR T therapy, Zola cell, and has also paused some trials as a result. We'll also discuss the White House's latest announcement regarding Trump's most favored nation drug pricing. After signing with most big pharmas, the administration has now struck deals with several large biotechs. We'll also touch on Revolution Medicine's breakthrough approval for pancreatic cancer, Beyond Tech's cancer vaccine flop, Wyonua's worse than expected data, and a handful of new biopharma deals, including Eli Lilly's latest spend. Let's dive in. Hi guys. Don't have all four of us today, but it's good to have you guys back. You each had short vacations around the weekend, and now, Annalie, your kids are back to school. Annalee Armstrong: Yes, I feel like I'm at full power. I'm coming Heather: Yeah. Annalee Armstrong: off a vacation. My kids are in school. It's great. Jef: I love it. Yes, they s we start Heather: Mm. And it's Jef: insanely early here. My kids have well, my older kid who goes to elementary school has been in school for a month now, hard to believe, almost a month. But I am glad that everyone else is starting to f like feel that normalcy of a fall routine. I like it. Annalee Armstrong: Yeah. Heather: Annalie, you're a little guy. It's his his first day of JK, right? How are you feeling? So sweet. Annalee Armstrong: Yeah, my little tiny he's four. He like I had to like lift him up onto the school bus today. It was very cute. It feels so and there like his backpack is too big for it's just so cute. Jef: I love that you guys have junior kindergarten. We don't have anything like that here. Heather: That's adorable. Jef: We do have like a pre K program for low income families, which is is really nice, but by and large, it's private Heather: Mm. Yeah. Jef: preschool or nothing around here. Annalee Armstrong: Yes, happy to have paid my final daycare bill for my kids last month. Woo! That's the biggest Jef: Ha ha ha. Heather: It's Annalee Armstrong: milestone here. Jef: Yes, absolutely. It was very cute scene. The two two Heather: So it's funny. Jef: brothers getting on the bus together. I love that they are Heather: Yeah. Jef: th he has his support from his older brother going off for his first year. Annalee Armstrong: Yeah. Heather: Yeah. It's funny, I never Jef: All right. Heather: went to JK but my brother did. So it I think that's it's kinda gone back and forth for several years. Annalee Armstrong: Yeah, yeah. And some people ch choose to just do another year a preschool or something. That still happens Heather: Hm. Hmm. Annalee Armstrong: in Canada, even though that's offered, you know. Jef: Nice to have options. Heather: Mm-hmm. Jef: All right, well let's dive into our show here. Let's get started with some intros. Heather, why don't you get us started? Heather: sure. I am Heather Mackenzie, Senior Editor at Biospace and I am responsible for Clinica Space, which hits your inboxes every Monday. Jef: Anally. Annalee Armstrong: I'm Annalie Armstrong, senior editor at Biospace. I am in charge of the Biofarm executive newsletter, and my dog has chosen this moment to come up here too. So Link Armstrong also here reporting for Biospace today. Heather: Yeah. Jef: He knew that you'd be lonely without your kids bothering you every five minutes. Annalee Armstrong: So true. Jef: All right. And again, I'm Jeff Ax, managing editor, and we are missing Gabrielle Mason today. She is in charge of our daily Gene Pool email and our weekly manufacturing brief. So definitely sign up for those as well. our first big news story of today is the Novartis and BMS trial pauses. hat tip to William Blair on this one. So we got a note Monday afternoon from Sammy Corwin and her colleagues about these adverse events and trial pauses before they'd ever been reported. So She and her colleagues picked up on these trial halts on clinical trial repositories, and one was actually stopped back in May. They reached out to Novartis and BMS who confirmed the news to them and subs subsequently to us as well. As we reported that the Novartis trial pauses stem from some patient deaths in their trials, which we'll discuss. And then BMS just had some Un unspecified safety concerns that cause them out of an abundance of caution to take a step back and pause these trials. These are for CAR T candidates in autoimmune disease. So let's start with the Novartis ones. Obviously, the bigger safety concern is those three patient deaths among patients who receive Novartis's CAR T candidate called Rap Cell. The cause of death was complications from serious immune effector cell associated hemophagocytic syndrome. I'm gonna call that I E C H S for short, a little bit easier to say. Heather: Good idea. that's a known side effect of CART therapies, right? Jef: Yeah, William Blair did note that. They said it's rare, but it has previously been reported with CD19 and BCMA CAR T therapies across blood cancer indications as well. Again, the trials we're talking about here are all autoimmune or I guess I should say immunology and neurology studies for Novartis. They did clarify, the company clarified that the cancer applications of this cell therapy have not been affected by the pause. Nevertheless, the company has paused several phase two autograph studies in various autoimmune conditions, plus phase one, two trials in rheumatory arthritis, generalized myosemia gravis, and certain types of multiple sclerosis as well. But as I said, Bristolmeyer Squib did pause some studies not due to deaths, and again, due to these less distinct safety concerns. They called them quote, transient and reversible inflammatory events associated with their own CART acid Zola cell. So at this point we're not totally clear on which BMS trials have been paused, but they are also in autoimmune indications. So William Blair said that these developments, both across Novartis and BMS, highlights this risk of CAR T and autoimmune and could potentially reduce competition in a crowded CAR T space. Heather: Wow, yeah, are there any clues yet as to why these safety events might have popped up in these autoimmune trials? Jef: Yeah, so clues, it's it's not clear, a lot of questions at this point, but William and Blair did speculate that it could have to do with the rapid manufacturing that was used for both RAP cell and zola cell. The analysts suggested that this process could be driving increased cell expansion and and thus the reported toxicities. But they also talked about other potential ideas, including the idea that autoimmune patients may just be predisposed to a hyperinflammatory state. So again, a lot of questions, more questions than answers at this point. these Deaths and pauses were not disclosed directly by the companies. They were not announced. It was just something that, like I said, William Blair picked up on the changes in the clinical trial repositories, reached out for confirmation. We subsequently did as well, and and we now have confirmation that this has all been paused, but there is still no direct release from the companies providing much more information. Heather: That's super sleuthing from William Blair, but it doesn't really indicate to to me that the system is working as efficiently as it could. Jef: Right, exactly. Yeah. So something we'll keep an eye out for more detail on and report as we get it. But for now, we'll move on to our sep second topic. we need to talk about Trump's most favored nation drug pricing. Again, it's been a little while since we talked about this topic. So just a re a refresher. many of industry's largest companies, you know, including Eli Lilly, Novo Nordist, Andron, Sonofi, Novartis, BMS, the companies we were just talking about, and on and on. These big farmers have struck deals with the White House to lower drug prices, to bring them in line in the US with other developed nations, and also to bring manufacturing to US soil. this is often to avoid tariffs or other repercussions from the administration. So while MFN, most favored nation, was at one point considered a major overhang for the industry, it kind of has faded into the background as these big farmers have not reported significant impacts of these deals to their businesses. So now the administration is moving down the ladder, this time striking deals with nine mid-size companies. In total, according to the White House, MFDN deals now cover some eighty-nine percent of the branded drug market. Annalee Armstrong: Yeah, so among the companies that have now signed on to this include Estellus Pharma, B1 Medicines, UCB, and Teva. the companies have collectively committed nearly $20 billion in manufacturing investments in the US. the White House announced at the same time. So that brings the full coverage of MFN to about 89% of branded drugs in the US. analysts have said that the agreements were you know, a positive move for these companies and could shield them from, you know, some tariff concerns, some other initiatives of the White House, but it also could take them out of contention for an upcoming Medicaid demonstration program that is kind of attempting to do the same thing as what MFN does, which is make prices the same with comparable nations elsewhere. But yeah, this really felt like deja vu having MFN come back. It's been a minute since we had to talk about this. But we always kind of knew this was coming. I know that earlier this year I sat down with Acadia pharmaceutical CEO, Katherine Owen Adams. And she told me that as a the CEO of a small biotech, she and other CEOs were working with the White House because they knew this was coming. they knew that eventually they would likely come under scrutiny from the White House. So they were trying to be proactive at that time. So now we see maybe like a tier of companies above them in terms of valuation, these agreements with the Trump administration. So we still haven't seen a plan for small biotechs, but we are seeing kind of this upper tier in terms of valuation in the industry signing deals with the White House. but it definitely seems that the all signals are suggesting that this isn't going away, that the White House would like to apply this to a broader swath of the industry. Swath? Swatch, swat. Jef: That sounds good to me. No, you're right. They they are definitely moving on down. you know, hitting almost ninety percent of brained drugs at this point. Maybe those smaller biotechs won't have to deal with this, but you know, definitely something we'll watch and you know, I would not be surprised if we see more announcements of this nature. Alright, well now moving on to the some positive clinical news. Revolution Medicine. So this company has been on everyone's radar since at least since April, if not previously. At that point, the company's RAS inhibitor doubled survival in advanced pancreatic cancer. So after that readout, everybody has been excited to hear and watch what Revolution Medicines it will bring next and and to watch this drug application at the FDA. And we weren't actually expecting a decision from FDA for another six months, but the FDA granted approval of the drug way ahead of schedule. And so this pancreatic cancer drug will now be known as you guys can help me with this pronunciation, Razonc or Razanok or Razonq. Okay. Annalee Armstrong: We cannot help you with this pr pronunciation. Heather: Yeah, me neither. I've been calling it Razon Q, but don't know if that's right. but this decision came down last Wednesday, shortly after this podcast aired. and this is huge for both for patients with with the the deadly cancer of course, but also for the rest of RevMed's pipeline, which includes more possible indications for the drug, Raz on Q. first line pancreatic cancer is one they're going for, as well as non-small cell lung cancer, another huge indication. And then they also have other solid tumors listed on their website. Truist even made a bold prediction. they said the company remains on course to emerge as the next oncology titan. So no wonder they wouldn't let Merck buy them. Jef: No w Yeah, I was just about to say the same thing. Exactly. Yeah. No, they're gonna s they're gonna be one of those biotechs kind of sticks it out on their own, which we've been seeing more and more of recently, these companies take you know, moving on to the commercial stage of drug development. So we'll keep watching. Heather: Yeah. Jef: yeah, I that's a bold bold prediction for them to become the next oncology titan, but definitely one to watch. Heather: It's like Merc, we don't need your thirty three billion or whatever, but we're gonna be the Jef: Ha ha. Heather: next Merc. Jef: Well, unfortunately the news in the cancer space was not all positive last week. So we had this great approval in the pancreatic cancer space, but we had bad news from Beyond Tech, which discontinued a phase two trial of one of their cancer vaccines in colorectal cancer after a independent data data safety monitoring board recommended the discontinuation because they thought the trial would be futile. Heather: Yeah, this is kind of a surprise partly because a a previous trial that they ran in pancreatic cancer as a phase one did really well. but we'll talk about that in a minute. BEMO analysts suggested that this result could raise questions about whether vaccine induced immune responses can prevent recurrence without also being combined with concurrent checkpoint inhibition or chemotherapy. So this of course, you know, almost immediately follows on Merck and Moderna's positive phase three trial in melanoma. Jef: Right, which had us so positive about this space. Heather: yeah, w to the point where I'm writing an article about the whole mRNA Jef: Yeah. Heather: space, but and that will be out next week. but but yeah, so BioNTech is also studying the personalized immunotherapy as they they call it, along with Roche's Techcentric. which is a checkpoint inhibitor, in a phase two trial for pancreatic cancer. And in April they reported really positive data. they said that nearly ninety percent of trial participants whose immune systems responded to the vaccine or or immunotherapy, were still alive up to six years after receiving the combo. Then pancreatic cancer, that's that's really something. Jef: Exactly, yeah. Okay, so we'll continue to watch that one in pancreatic cancer, but for now the colorectal cancer indication is off the table, it seems. All right, next up on our list we have here Winua. So we learned in July that this TTR silencer from AstraZeneca and Ionis failed to show significant cardiovascular benefit in a phase three study of patients with ATTR cardiomyopathy. This past weekend at the European Society of Cardiology, we got some more detail on that failure and it was worse than expected, to say the least. Heather: Yeah, it's pretty bad. so Wainua is already approved in ATTR polyneuropathy or ATTRPN. so it was widely expected to also work in ATTR CM. but as we learned in July, the trial results did not support that assumption. so we've now learned that the hazard ratio in the trial was one point one four. And that means that patients had a 14% higher rate of cardiovascular mortality and recurrent clinical events compared with the comparator arm. So stifle called the result clearly worse than expected. Interestingly though, there was a 29% improvement in cardiovascular events for patients who received voyula by itself. so this made Oppenheimer wonder about potential safety signals for Wainua when combined with an anti sense oligonucle oligonucleotide my turn stabilizer. Jef: Yeah, no, that is interesting differentiation between the monotherapy and the combo. So that's that's something to look further into. but whenever one of these readouts comes out, we get a lot of notes from analysts. People are watching this space very closely, and there are a lot of knock-on effects throughout the ATT RCM space, especially from this Wainua surprise failure. Heather: Yeah, that's right. for starters, Jeffrey said Jeffrey's said that the new data mean oral stabilizers from Bridge Bio and Pfizer will likely remain the preferred first line option for ATTR CM. alnylum on the other hand also has an ATTR CM drug on the market and it's a TTR silencer like Wynua. But Stifle said they don't see a commercial impact for this drug. rather they pointed to potential shifts in Al Nylum's ongoing phase three program for its next gen RNAI therapy. for this one, Stifle said the company could direct further enrollment toward monotherapy and make results from that group the primary outcome. Jef: Yeah, I mean certainly learn from others' failures if you can and improve the outcomes for patients. So another space, lots of open questions here that we will continue to watch. All right, last item on our agenda today is to recap some deals for you. So let's start with Eli Lilly, this year's all-time biggest deal maker. This week the pharma announced its attended acquisition of Merida Biosciences for up to nearly three billion. Annalee Armstrong: Yeah, so we haven't done an update on Lily's deal activity since the half. but at that point we had tallied about $25 billion in deal activity. So here we can add another three billion and a couple more, because I think they've had more since I did that analysis. But yeah, so Merida Merit Merita Biosciences will bring to Lily a phase one asset in inflammation and immunology. this asset is under development for thyroid eye disease and Graves disease. So analysts were you know pretty keen on this deal. They said that it would help diversify Lily's I and I portfolio and complement some earlier deal activity that they've already done in this space. So if you remember any of the deals that Lily has done, of which there have been many this year, they bought Ventix Biosciences and Repertoire earlier this year. Both of them were in that I and I space. So they are really trying to fill up this portion of their pipeline. Jef: INI is still so hot. We've covered it a bunch in the last couple of years. It's definitely an area companies are targeting, in particular because they think they can get pipeline and a product out of it. You know, there's a lot of these products that are being tested in a variety of INI indications. So Lily is not alone in that. another big deal maker we've been tracking recently is Roche. So this is not an acquisition, but a number of partnerships all coming out of Asia for Roche, including two just in the past week. Annalee Armstrong: Yes, absolutely. Their business team over there has been very busy. so today we heard that they signed a partnership with SemSear Zyming that could be worth up to $1.5 billion. The partners are gonna work together on a T cell engager for B cell mediated diseases. This includes certain types of lymphoma. so that is the kind of the latest partnership. But there's also they also signed one last week with Duality Bio to work on an antibody drug conjugate. And there was a third, y you know, so these are like billions of dollars worth of commitments that Roche is putting down over there. so clearly showing that the interest in biotechs across Asia is just absolutely not going anywhere. Jef: Agreed. All right. Well now to wrap up our show, as we often do, can you tell us a little bit about what we can see in Bio Pharma Executive this week? Annalee Armstrong: Yes, definitely. I know Gabby is not here, but she has been very busy leading up to her vacation, writing a ton of really, really great stories for Biofarm Executive. She's been doing a lot of digging on the deal environment in general when it comes to IPOs, reverse mergers, that kind of thing. So we have a really deep dive into reverse mergers that has published today, as you're listening to this on Wednesday. and she has also updated her weekly IPO tracker and done some reporting there. And then we also have a piece looking at BMS's future after the AstraZeneca mega merger, which never materialized. Jef: Yeah, that one's a really interesting piece as well. Obviously, everybody was talking about the potential for a BMS AstraZeneca merger when, you know, reports of those rumors broke out. But to take a closer look at what BMS is facing, I mean, we covered it at the time with facing these patent cliffs and declining revenue and what is BMS's plan. AstraZeneca seemed like a potential merger with AstraZeneca seemed like a potential good option. Analysts were generally thinking that. if that mega merger were to materialize that it would be to BMS's favor in particular. So yeah, what is their plan now? It's a very very interesting read. So check that out. And that's our show for today. Thank you all for listening and check back with us next week as always. And please subscribe on all your favorite podcast channels.